麝香化瘀醒脑颗粒对脑出血大鼠脑组织TLR4/MyD88/NF-κB信号通路的影响OA
Impact of Shexiang Huayu Xingnao Granule on TLR4/MyD88/NF-κB signal pathway in brain tissue of rats with intracerebral hemorrhage
目的 探讨麝香化瘀醒脑颗粒治疗脑出血(ICH)的潜在作用机制.方法 30 只SD雄性大鼠,随机选取 6 只为假手术组(Sham组),剩余大鼠构建ICH大鼠模型,造模成功大鼠随机分为模型组(ICH组)、麝香化瘀醒脑颗粒组(SXHY组),每组各 6 只.对各组大鼠进行神经行为学评分和HE染色评价脑损伤;酶联免疫吸附(ELISA)检测血清中炎症因子γ干扰素(IFN-γ)、肿瘤坏死因子-α(TNF-α)、脑源性神经营养因子(BDNF)和白细胞介素-6(IL-6)的表达水平;采用免疫荧光双染观察血肿周围脑组织小胶质细胞表达与分布情况;蛋白质印迹(Western blot)检测Toll样受体 4(TLR4)、髓分化因子(MyD88)、磷酸化核因子-κB p65(p-NF-κB p65)、核因子-κB p65(NF-κB p65)蛋白的表达水平.结果 麝香化瘀醒脑颗粒能够显著改善ICH模型大鼠的神经功能损伤症状,减少脑组织病变,降低IFN-γ、TNF-α和IL-6表达水平,升高BDNF表达水平(P＜0.01);降低M1 型小胶质细胞和升高M2 型小胶质细胞活化,降低TLR4、MyD88、p-NF-κB p65 蛋白表达,升高NF-κB p65 蛋白表达(P＜0.01).结论 麝香化瘀醒脑颗粒可有效减少ICH大鼠炎症因子的释放,促进小胶质细胞从M1 型转向M2 型,可能是通过调控TLR4/MyD88/NF-κB信号通路实现对ICH的治疗作用.
Objective To investigate the potential function mechanism of Shexiang Huayu Xingnao Granule in the treatment of intracerebral hemorrhage(ICH).Methods A total of 30 SD male rats were randomly selected as the Sham operation group(Sham group,n=6),and the remaining rats were used to build rat models of ICH.After successful modeling,they were randomly divided into the model group(ICH,n=6)and the Shexiang Huayu Xingnao Granule group(SXHY group,n=6).The rats in each group were evaluated by neurobehavioral score and HE staining.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression levels of inflammatory factors such as interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),brain-derived neurotrophic factor(BDNF)and interleukin-6(IL-6)in serum.The expression and distribution of microglial cells in brain tissue around hematoma were observed by immunofluorescence double staining.The expression levels of Toll-like receptor 4(TLR4),myeloid differentiation primary response protein(MyD88),phosphorylated nuclear factor-κB p65(p-NF-κB p65)and nuclear factor-κB p65(NF-κB p65)were detected by protein Western blot method.Results Shexiang Huayu Xingnao Granule can significantly improve the symptoms of neurological impairment in ICH model rats,reduce brain pathological changes,reduce the expression levels of IFN-γ,TNF-α and IL-6,and increase the expression level of BDNF(P＜0.01).It decreased the activation of M1 microglial cells and increased the activation of M2 microglial cells,decreased the expression of TLR4,MyD88 and p-NF-κB p65,and increased the expression of NF-κB p65(P＜0.01).Conclusion Shexiang Huayu Xingnao Granule can effectively reduce the release of inflammatory factors in ICH rats,and promote the transformation of microglial cells from M1 type to M2 type,which may be achieved by regulating TLR4/MyD88/NF-κB signaling pathway.
郑直;李双阳;张建磊;王凌雪;吴英
四川省泸州市人民医院骨科,四川 泸州 646000西南医科大学附属中医医院神经内科,四川 泸州 646000西南医科大学附属中医医院神经内科,四川 泸州 646000西南医科大学附属中医医院神经内科,四川 泸州 646000西南医科大学附属中医医院神经内科,四川 泸州 646000
医药卫生
脑出血麝香化瘀醒脑颗粒小胶质细胞炎症因子TLR4/MyD88/NF-κB
Intracerebral hemorrhageShexiang Huayu Xingnao GranuleMicroglial cellsInflammatory factorsTLR4/MyD88/NF-κB
《中国医药科学》 2025 (1)
4-7,4
四川省中医药管理局项目(2023MS014).
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